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Biomedical subjects

K Jungermann

Publications and source records attributed to K Jungermann.

At least 109 records · Page 6Linked to original sources
PubMed1991

Eicosanoid-mediated increase in glucose and lactate output as well as decrease and redistribution of flow by complement-activated rat serum in perfused rat liver.

Rat serum, in which the complement system had been activated by incubation with zymosan, increased the glucose and lactate output, and reduced and redistributed the flow in isolated perfused rat liver clearly more than the control serum. Heat inactivation of the rat serum prior to zymosan incubation abolished this difference. Metabolic and hemodynamic alterations caused by the activated serum were dose dependent. They were almost completely inhibited by the cyclooxygenase inhibitor indomethacin and by the thromboxane antagonist 4-[2-(4-chlorobenzesulfonamide)-ethyl]-benzene-acetic acid (BM 13505), but clearly less efficiently by the 5'-lipoxygenase inhibitor nordihydroguaiaretic acid and the leukotriene antagonist N-(3-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-propoxy]-4-chlorine-6-meth yl- phenyl)-1H-tetrazole-5-carboxamide sodium salt (CGP 35949 B). Control serum and to a much larger extent complement-activated serum, caused an overflow of thromboxane B2 and prostaglandin F2 alpha into the hepatic vein. It is concluded that the activated complement system of rat serum can influence liver metabolism and hemodynamics via release from nonparenchymal liver cells of thromboxane and prostaglandins, the latter of which can in turn act on the parenchymal cells.

Animals↗
PubMed1991

Distribution of cyclic AMP phosphodiesterase in microdissected periportal and perivenous rat liver tissue with different dietary states.

Cyclic AMP phosphodiesterase was measured in liver homogenates and microdissected periportal and perivenous liver tissue from rats in different dietary states under different conditions of substrate saturation and effector stimulation. A radiochemical microtest, more sensitive by 2-3 orders of magnitude than the usual assay, was established for the determination of the activity in liver samples corresponding to 200-800 ng dry weight. At saturating cyclic AMP concentrations (46 microM) phosphodiesterase was homogeneously distributed within the liver acinus of fed rats. Starvation for 48 h led to a decrease in the overall activity and to a heterogenous distribution with slightly higher activities in the perivenous zone. At physiological cyclic AMP concentrations (1.8 microM) phosphodiesterase showed a flat zonal gradient in livers of fed rats with higher levels in the periportal zone; after 48 h starvation it was homogeneously distributed. In the presence of cyclic GMP (2 microM) the basal activity at physiological substrate concentrations was stimulated to a greater extent in the perivenous zone. This led to a homogeneous activity distribution in the fed state and to a heterogenous pattern with a slight perivenous maximum in the fasted state. Thus there was no or only a small zonal heterogeneity of signal transmitting enzymes such as cyclic AMP phosphodiesterase and glucagon-stimulated adenylate cyclase (Zierz and Jungermann 1984). This similar signal transducing capacity in the periportal and the perivenous area will contribute to maintain the zonation of signal input due to the hormone concentration gradients across the liver acinus.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Control of glycogenolysis and blood flow by arterial and portal norepinephrine in perfused liver.

In isolated rat liver single pass perfused via both the hepatic artery (80 mmHg, 30% flow) and the portal vein (10 mmHg, 70% flow), norepinephrine (NE) was infused either singly or jointly via the hepatic artery or the portal vein in the absence or presence of the alpha 1-blocker prazosin or the beta 2-blocker butoxamine. Arterial NE caused an increase in glucose output and a shift from lactate uptake to release that was slower in onset and smaller in peak height but longer in duration than the alterations affected by portal NE. The sum of the metabolic changes by arterial and portal NE was not equal to the changes by jointly applied arterial plus portal NE. The metabolic alterations by arterial NE were mediated via alpha 1-receptors, with beta 2-receptors probably having a permissive function, but those by portal NE were transmitted only via alpha 1-receptors. Arterial NE caused a strong decrease in arterial flow and contralaterally also a smaller reduction of portal flow. Portal NE decreased portal flow but did not significantly influence arterial flow. The sum of the alterations in flow by arterial and portal NE was not equal to the changes by jointly applied NE. The hemodynamic alterations in the artery by arterial NE were the results of actions via alpha 1-receptors and counteractions via beta 2-receptors, whereas the changes in the portal vein by arterial NE and portal NE were mediated via alpha 1-receptors. About 65% of arterial and only 30% of portal NE was extracted during a single path. The results indicate that the hepatic artery and the portal vein can function as independent sites of hormonal signal input, which interact by complex but still undefined mechanisms in the regulation of metabolism and hemodynamics.

Animals↗
PubMed1991

Increase in glucose and lactate output and perfusion resistance by stimulation of hepatic nerves in isolated perfused rat liver: role of alpha 1-, alpha 2-, beta 1- and beta 2-receptors.

Rat liver was perfused in situ via the portal vein without recirculation: 1) Electrical stimulation of the nerve bundles around hepatic artery and portal vein increased glucose and lactate output, reduced flow and caused an overflow of noradrenaline into the hepatic vein. The alpha-agonist phenylephrine also augmented glucose and lactate output and lowered flow with an ED50 of about 1 microM, while the beta-agonist isoproterenol increased glucose output but reduced lactate output with an ED50 of about 0.2 microM and left flow unaltered. 2) The alpha 1-receptor antagonist prazosin (KI at alpha 1-sites approximately 1 nM, at alpha 2-sites approximately 100 nM) inhibited the nerve stimulation-dependent increase in glucose and lactate output and reduction of flow with an ID50 of about 1 nM, while the alpha 2-receptor antagonist yohimbine (KI at alpha 2-sites approximately 10 nM, at alpha 1-sites approximately 1500 nM) was inhibitory only with an ID50 of about 400 nM. 10 nM prazosin clearly reduced the nerve actions, completely blocked the effects of 1 microM phenylephrine and left the effects of 0.2 microM isoproterenol unaltered. 10 nM yohimbine did not affect the nerve actions nor the effects of phenylephrine or isoproterenol. 3) The beta 1-receptor antagonist metoprolol (KI at beta 1-sites approximately 100 nM, at beta 2-sites approximately 1.2 microM) at 10 microM concentrations did not interfere with the nerve stimulation-dependent increase in glucose and lactate output or the decrease in flow. It did not have any specific alpha-antagonistic influence either on the changes brought about by 1 microM phenylephrine; however, it blocked the beta 2-mediated increase in glucose output by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Unspecific inhibition by the calmodulin antagonist calmidazolium and the intracellular calcium antagonist TMB-8 of the actions of sympathetic hepatic nerves and noradrenaline on glucose balance and flow in perfused rat liver.

In perfused rat liver hepatic nerve stimulation (10 Hz, 2 ms) (NS) increased glucose and lactate output, decreased flow and was accompanied by an overflow of noradrenaline into the hepatic vein. These effects were dependent on extracellular and partly on intracellular calcium. Infusion of noradrenaline (1 microM) (NA) elicited similar effects. 1) Calmidazolium at 1, 2 and 5 microM caused an increase in basal glucose output and a decrease and intrahepatic redistribution of flow after a lag of 30, 20 and 5 min, respectively. 2) After 5 min of 1 microM calmidazolium, i.e. before it altered basal metabolism and flow, the actions of NS and NA remained unaltered. 3) After 40 min of 1 microM calmidazolium, i.e. after it had just begun to alter basal metabolism and flow, NS caused a decrease in glucose and lactate output rather than an increase and the metabolic effects of NA were strongly reduced whereas the hemodynamic changes of both stimuli were not altered. 4) TMB-8 at 25, 50 and 100 microM caused a transient increase in lactate output and a decrease and intrahepatic redistribution of flow after a lag of 5 min only at 100 microM concentrations. 5) The effects of NS were inhibited already by 25 microM TMB-8 which reduced NA release whereas the effects of NA were not influenced. Thus, calmidazolium and TMB-8 did not act as a calmodulin and intracellular calcium antagonist, respectively, but had unspecific "side effects" in the complex system of the perfused liver. The antagonists cannot be used to study the role of intracellular calcium in intact organs.

Animals↗
PubMed1990

Differential control of glycogenolysis and flow by arterial and portal acetylcholine in perfused rat liver.

The effects of acetylcholine on glucose and lactate balance and on perfusion flow were studied in isolated rat livers perfused simultaneously via the hepatic artery (100 mmHg, 25-35% of flow) and the portal vein (10 mmHg, 75-65% of flow) with a Krebs-Henseleit bicarbonate buffer containing 5 mM-glucose, 2 mM-lactate and 0.2 mM-pyruvate. Arterial acetylcholine (10 microM sinusoidal concentration) caused an increase in glucose and lactate output and a slight decrease in arterial and portal flow. These effects were accompanied by an output of noradrenaline and adrenaline into the hepatic vein. Portal acetylcholine elicited only minor increases in glucose and lactate output, a slight decrease in portal flow and a small increase in arterial flow, and no noradrenaline and adrenaline release. The metabolic and haemodynamic effects of arterial acetylcholine and the output of noradrenaline and adrenaline were strongly inhibited by the muscarinic antagonist atropine (10 microM). The acetylcholine-dependent alterations of metabolism and the output of noradrenaline were not influenced by the alpha 1-blocker prazosin (5 microM), whereas the output of adrenaline was increased. The acetylcholine-dependent metabolic alterations were not inhibited by the beta 2-antagonist butoxamine (10 microM), although the overflow of noradrenaline was nearly completely blocked and the output of adrenaline was slightly decreased. These results allow the conclusion that arterial, but not portal, acetylcholine caused sympathomimetic metabolic effects, without noradrenaline or adrenaline being involved in signal transduction.

Acetylcholine↗
PubMed1990

Metabolic actions of insulin-like growth factor-I in cultured hepatocytes from adult rats.

Short-term and long-term regulation of hepatic carbohydrate metabolism by insulinlike growth factor-I was studied in primary cultures of adult rat hepatocytes and compared with the metabolic potency of insulin. Insulinlike growth factor-I stimulated the formation of [14C]lactate from [14C]glucose up to three-fold with a half-maximally effective concentration of approximately 50 nmol/L. Basal glycogenolysis was inhibited by about 20%, and glucagon-activated glycogenolysis was blocked completely by insulinlike growth factor-I with half-maximally effective concentrations of about 1.5 to 2 nmol/L. The activity of the key glycolytic enzymes glucokinase and pyruvate kinase were induced twofold. The glucagon-dependent induction of phosphoenolpyruvate carboxykinase--the key gluconeogenic enzyme--was antagonized with a half-maximally effective concentration of about 5 nmol/L. This inhibition of the glucagon-dependent induction of the enzyme was accompanied by a similar reduction of the increase in phosphoenolpyruvate carboxykinase-mRNA level as assessed by Northern blot analysis. The potency of insulinlike growth factor-I at half-maximally effective concentrations was approximately 2% to 4% that of insulin. Because binding studies demonstrated a comparably low affinity of insulinlike growth factor-I to the insulin receptor, it is suggested that in adult liver--in contrast to fetal and regenerating liver--insulinlike growth factor-I could exert short-term and long-term metabolic effects on parenchymal cells only through interaction with the insulin receptor.

Animals↗
PubMed1990

Predominant periportal expression of the phosphoenolpyruvate carboxykinase and tyrosine aminotransferase genes in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization.

The zonal distribution of phosphoenolpyruvate carboxykinase (PCK) and tyrosine aminotransferase (TAT) mRNA in liver was studied by in situ hybridization with radiolabelled cRNA probes and the abundance of PCK and TAT mRNA was quantified by Northern blot analysis of total RNA with biotinylated cRNA probes. Livers were taken from rats during a normal 12 h day/night rhythm, when they had access to food only during the dark period from 7 pm to 7 am, or during refeeding, when they had access to food after having been starved for 60 h. 1. Daily feeding rhythm: High levels of PCK mRNA were distributed mainly in the periportal and intermediate zone during the fasting period at noon and 6 pm. Feeding caused a rapid decrease in PCK mRNA level and a restriction of PCK mRNA localization to the periportal area within the first 2 h. No further alterations were observed during the following hours of the feeding period. TAT mRNA was distributed also in the periportal and intermediate zone during the fasting period. Feeding first reduced the mRNA level without changing the distribution pattern. Then towards the end of the feeding period TAT mRNA increased again to half-maximal levels and became restricted mainly to the periportal area. 2. Starvation-refeeding cycle: High amounts of PCK mRNA as well as of TAT mRNA were localized predominantly in the periportal and intermediate zone after 60 h of starvation. PCK and TAT mRNA both decreased markedly during the first 2 h of refeeding and then remained almost constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Activation of glycogenolysis by stimulation of the hepatic nerves in perfused livers of guinea pig and tree shrew as compared to rat: differences in the mode of action.

A study on the metabolic and hemodynamic actions of hepatic nerve stimulation in the perfused liver of guinea pig and tree shrew as compared to rat was performed, since the density of liver innervation was reported to be different. 1) Nerve stimulation resulted in an increase in glucose release and decrease in lactate uptake or in a shift to output as well as a decrease in portal flow in all three species. The change in glucose output was very similar, that in lactate balance and flow was smaller in tree shrew than in guinea pig and rat. Apparently, the metabolic and hemodynamic changes did not reflect the different densities of liver innervation. 2) The overflow of the neurotransmitter noradrenaline into the hepatic vein differed very clearly in the three animals. In the guinea pig and tree shrew the maximal increase in noradrenaline concentration measured in the effluent was about 6-7-fold higher than in the rat. 3) The content of noradrenaline in the liver in vivo was about five-fold higher in the guinea pig and again another four-fold higher in the tree shrew than in the rat. The contents of adrenaline and dopamine were very low in comparison to those of noradrenaline. The different hepatic noradrenaline contents of the three species investigated are in line with the anatomical findings on the different innervation density. 4) Inhibitors of eicosanoid synthesis reduced the nerve stimulation-dependent metabolic and hemodynamic alterations in guinea pig liver as in rat liver indicating a similar mechanism in these species. Apparently, prostaglandins might be involved as mediators or modulators of nerve actions also in the more densely innervated guinea pig liver and not only in the less densely innervated rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗
PubMed1990

Mechanism of the inhibition by insulin of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. Action on gene transcription, mRNA level and -stability as well as hysteresis effect.

The mechanism of the antagonistic action of insulin on the glucagon-dependent stimulation of the phosphoenolpyruvate carboxykinase (PEPCK) gene was studied in primary cultures of rat hepatocytes. Gene expression was monitored by the transcriptional activity of the PEPCK gene and the accumulation and degradation of PEPCK mRNA. 1) Insulin in concentrations from 0.1 to 100nM shifted the dose-response curve of the glucagon-dependent accumulation of PEPCK mRNA to the right, increasing the half-maximally effective glucagon concentration gradually from 0.1 to 0.7nM. At saturating 10nM glucagon concentrations insulin was not antagonistic. 2) Glucagon at 0.1nM concentrations increased PEPCK gene transcription and PEPCK mRNA to a transient maximum at 0.5 and 2 h, respectively. Insulin, added at 10nM concentrations simultaneously with glucagon, reduced the maximal increase in PEPCK gene transcription by 70% and in PEPCK mRNA by 45%, respectively. 3) Following the maximal glucagon-induced increase after 2 h PEPCK mRNA declined to half-maximal levels after another 2.3 h. Insulin, added at 2 h at the PEPCK mRNA maximum, accelerated the disappearance of PEPCK mRNA, which reached half-maximal values already after another 1.2 h. 4) The transcriptional inhibitor cordycepin, added at 2 h at the PEPCK mRNA maximum, clearly retarded the normal and the insulin-accelerated decay of PEPCK mRNA so that half-maximal levels were reached only after another 5 h and 3 h, respectively. However, cordycepin did not retard the decay of PEPCK mRNA, when insulin was present from the beginning of induction by glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Modulation by oxygen of the actions of noradrenaline, sympathetic nerve stimulation and prostaglandin F2 alpha on carbohydrate metabolism and hemodynamics in perfused rat liver.

Rat liver was perfused in situ via the portal vein without recirculation of the perfusate. The perfusion medium contained 5mM glucose, 2mM lactate and 0.2mM pyruvate, and it was equilibrated with different oxygen concentrations so as to vary the rate of oxygen delivery from 4 (normal) to either 12 or 0 mumol x min-1 x g-1 (U/g). 1) Basal glucose and lactate output were clearly increased, when oxygen delivery and therefore uptake were decreased from 4 to 2 and 0 U/g. 2) Noradrenaline caused a marked increase in the output of glucose and lactate and a slight increase in oxygen uptake; it also decreased the rate of flow of the perfusate. Decrease of the oxygen supply did not affect this alteration in the glucose and lactate balance, but it abolished the increase in oxygen uptake and decreased the magnitude of the effect on the perfusion rate. 3) Sympathetic nerve stimulation strongly increased glucose and lactate output and clearly reduced oxygen uptake and perfusate flow. Decreased oxygen delivery caused a decrease in the magnitude of all these changes. 4) Prostaglandin F2 alpha increased glucose and lactate release and decreased perfusate flow. Decrease of the oxygen supply did not affect the increased glucose and lactate release, but it decreased the magnitude of the effect on the perfusion rate. These results lead to the following major conclusions. Oxygen strongly regulates basal carbohydrate metabolism, while it does not affect the metabolic actions of noradrenaline and prostaglandin F2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Relative contribution of glycogenolysis and gluconeogenesis to basal, glucagon- and nerve stimulation-dependent glucose output in the perfused liver from fed and fasted rats.

The relative contribution to basal, glucagon- and nerve stimulation-enhanced glucose output of glycogenolysis (glucose output in the presence of the gluconeogenic inhibitor mercaptopicolinate) and gluconeogenesis (difference in glucose output in the absence and presence of the inhibitor) was investigated in perfused livers from fed rats with high and from fasted animals with low levels of glycogen. 1) Basal glucose output in both states was due only to gluconeogenesis. 2) Glucagon-enhanced glucose output was due about equally to glycogenolysis and gluconeogenesis in the fed state, but predominantly to gluconeogenesis (80%) in the fasted state. 3) Nerve stimulation-increased glucose output was due mainly to glycogenolysis (65%) in the fed state and about equally to both processes in the fasted state. The results suggest that under basal conditions of normal demands the liver supplies glucose only via gluconeogenesis and thus spares its glycogen stores, and that in situations of enhanced demands signalled by an increase in glucagon or sympathetic tone the liver liberates glucose mainly via glycogenolysis.

Animals↗
PubMed1990

Role of extracellular calcium in the metabolic and hemodynamic actions of sympathetic nerve stimulation, noradrenaline and prostaglandin F2 alpha in perfused rat liver. Differential inhibition by nifedipine and verapamil.

In perfused rat liver hepatic nerve stimulation (10 Hz, 2 ms) caused an increase in glucose and lactate output, a decrease in flow and an overflow of noradrenaline into the hepatic vein. Noradrenaline (1 microM) (NA) and prostaglandin F2 alpha (5 microM) (PGF2 alpha), which are implicated as mediators of nerve action, elicited similar effects. 1) All actions of nerve stimulation and the hemodynamic but not the metabolic effects of noradrenaline and PGF2 alpha were largely dependent on extracellular calcium. 2) The dihydropyridine type calcium antagonist nifedipine (5 microM) inhibited the hemodynamic but not the metabolic actions of nerve stimulation, NA and PGF2 alpha, while the phenylalkylamine type calcium antagonist verapamil (5 microM) had no effect. These findings allow the following conclusions: Calcium influx into I nerve endings, necessary for the release of neurotransmitter, II parenchymal cells, for the display of metabolic effects induced by nerve stimulation, and III the actions of NA and PGF2 alpha, do not appear to be mediated by the normal affinity nifedipine- or the verapamil-sensitive channels. Calcium influx into vascular smooth muscle and/or endothelial cells for the display of hemodynamic action induced by nerve stimulation and the NA and PGF2 alpha effects, appear to occur through nifedipine-sensitive but verapamil-insensitive channels.

Animals↗
PubMed1989

Direct activation by prostaglandin F2 alpha but not thromboxane A2 of glycogenolysis via an increase in inositol 1,4,5-trisphosphate in rat hepatocytes.

In rat liver prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TXA2), released from non-parenchymal cells, have been implicated as mediators of the enhancement of glucose and lactate output from parenchymal cells caused by sympathetic nerve stimulation [Iwai, M. et al. (1988) Eur. J. Biochem. 175, 45-50]. In isolated rat hepatocytes PGF2 alpha, of which 75% were degraded within 10 min, but not the TXA2 analogue U46619 increased inositol 1,4,5-trisphosphate (IP3), glycogen phosphorylase a activity and glucose output like noradrenaline and vasopressin; cyclic AMP remained unaltered. The maximal increase in IP3 was reached within 20 s and in phosphorylase activity as well as glucose release within 1 min. The results indicate that only PGF2 alpha but not TXA2 can play a role as a direct mediator of the sympathetic metabolic nerve actions in rat liver and that hepatocytes contain also stimulatory prostaglandin receptors linked to phospholipase C in addition to the inhibitory receptors linked to adenylate cyclase known thus far.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Predominant localization of phosphoenolpyruvate carboxykinase mRNA in the periportal zone of rat liver parenchyma demonstrated by in situ hybridization.

In rat liver parenchyma, expression of the phosphoenolpyruvate carboxykinase (PEPCK) gene was studied by Northern blot analysis with a biotinylated cRNA probe and the zonal localization of PEPCK mRNA was demonstrated by in situ hybridization with a radiolabelled cRNA probe. During the feeding period at night, overall PEPCK mRNA levels were low and PEPCK mRNA was detected only in small areas of the periportal zone. At the beginning of the light period (7 am) the overall PEPCK mRNA level began increasing and the periportal areas containing PEPCK mRNA broadened. The maximum of the total abundance and of the area with high levels of PEPCK mRNA was reached at noon. Fasting for 24-72 h did not cause further significant alterations in the level or localization of PEPCK mRNA. The present data are in line with previous findings of the predominant localization of PEPCK activity and enzyme protein in periportal hepatocytes. They suggest that the heterogeneous expression of the PEPCK gene in rat liver is regulated at the pretranslational level.

Animals↗
PubMed1989

Mechanism of action of cysteinyl leukotrienes on glucose and lactate balance and on flow in perfused rat liver. Comparison with the effects of sympathetic nerve stimulation and noradrenaline.

Rat livers were perfused at constant pressure via the portal vein with media containing 5 mM glucose, 2 mM lactate and 0.2 mM pyruvate. 1. Leukotrienes C4 and D4 enhanced glucose and lactate output and reduced perfusion flow to the same extent and with essentially identical kinetics. They both caused half-maximal alterations (area under the curve) of carbohydrate metabolism at a concentration of about 1 nM and of flow at about 5 nM. The leukotriene-C4/D4 antagonist CGP 35949 B inhibited the metabolic and hemodynamic effects of 5 nM leukotrienes C4 and D4 with the same efficiency, causing 50% inhibition at about 0.1 microM. 2. Leukotriene C4 elicited the same metabolic and hemodynamic alterations with the same kinetics as leukotriene D4 in livers from rats pretreated with the gamma-glutamyltransferase inhibitor, acivicin. 3. The calcium antagonist, nifedipine, at a concentration of 50 microM did not affect the metabolic and hemodynamic changes caused by 5 nM leukotriene D4. The smooth-muscle relaxant, nitroprussiate, at a concentration of 10 microM reduced flow changes, without significantly affecting the metabolic alterations. 4. Leukotriene D4 not only reduced flow; it also caused an intrahepatic redistribution of flow, restricting some areas from perfusion. Thus, leukotrienes increased glucose and lactate output directly in the accessible parenchyma and, in addition, indirectly by washout from restricted areas during their reopening upon termination of application. 5. The phospholipase A2 inhibitor, bromophenacyl bromide, but not the cyclooxygenase inhibitor, indomethacin, at a concentration of 20 microM reduced the metabolic and hemodynamic effects of 5 mM leukotriene D4. 6. Stimulation of the sympathetic hepatic nerves with 2-ms rectangular pulses at 20 Hz and infusion of 1 microM noradrenaline increased glucose and lactate output and decreased flow, similar to 10 nM leukotrienes C4 and D4. The kinetics of the metabolic and hemodynamic changes caused by the leukotrienes differed, however, from those due to nerve stimulation and noradrenaline. 7. The leukotriene-C4/D4 antagonist, CGP 35949 B, even at very high concentrations (20 microM) inhibited the metabolic and hemodynamic alterations caused by nerve stimulation or noradrenaline infusion only slightly and unspecifically.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Increase of glucose and lactate output and decrease of flow by human anaphylatoxin C3a but not C5a in perfused rat liver.

The complement fragments C3a and C5a were purified from zymosan-activated human serum by column chromatographic procedures after the bulk of the proteins had been removed by acidic polyethylene glycol precipitation. In the isolated in situ perfused rat liver C3a increased glucose and lactate output and reduced flow. Its effects were enhanced in the presence of the carboxypeptidase inhibitor DL-mercaptomethyl-3-guanidinoethylthio-propanoic acid (MERGETPA) and abolished by preincubation of the anaphylatoxin with carboxypeptidase B or with Fab fragments of an anti-C3a monoclonal antibody. The C3a effects were partially inhibited by the thromboxane antagonist BM13505. C5a had no effect. It is concluded that locally but not systemically produced C3a may play an important role in the regulation of local metabolism and hemodynamics during inflammatory processes in the liver.

Anaphylatoxins↗